Protection against glucose‐induced neuronal death by NAAG and GCP II inhibition is regulated by mGluR3

  title={Protection against glucose‐induced neuronal death by NAAG and GCP II inhibition is regulated by mGluR3},
  author={Alison Berent-Spillson and Amanda M. Robinson and David Golovoy and Barbara S. Slusher and Camilo Rojas and James W. Russell},
  journal={Journal of Neurochemistry},
Glutamate carboxypeptidase II (GCP II) inhibition has previously been shown to be protective against long‐term neuropathy in diabetic animals. In the current study, we have determined that the GCP II inhibitor 2‐(phosphonomethyl) pentanedioic acid (2‐PMPA) is protective against glucose‐induced programmed cell death (PCD) and neurite degeneration in dorsal root ganglion (DRG) neurons in a cell culture model of diabetic neuropathy. In this model, inhibition of caspase activation is mediated… 

Metabotropic glutamate receptor 3 protects neurons from glucose‐induced oxidative injury by increasing intracellular glutathione concentration

Results support the conclusions that activating glial mGluR3 protects neurons from glucose‐induced oxidative injury by increasing free radical scavenging and stabilizing mitochondrial function, through increased GSH antioxidant defense.

Pretreatment with mGluR2 or mGluR3 Agonists Reduces Apoptosis Induced by Hypoxia-Ischemia in Neonatal Rat Brains

It is concluded that the neuroprotective effect of NAAG applied 1 h before HI is most likely the result of a combination of mGluR3 and NMDA receptor activation, whereas the beneficial effects of N AAG pretreatment can be explained by the activation of NMDA receptors and induction of the antioxidative/antiapoptotic defense system triggered by mild excitotoxicity in neurons.

Neuroprotective effect of N‐acetyl‐aspartyl‐glutamate in combination with mild hypothermia in the endothelin‐1 rat model of focal cerebral ischaemia

It is concluded that treatment with NAAG causes the same degree of neuroprotection as treatment with hypothermia, and combination of the two treatments, although reducing apoptosis, does not considerably improve ischaemic damage.

Selective CNS Uptake of the GCP-II Inhibitor 2-PMPA following Intranasal Administration

Glutamate carboxypeptidase II (GCP-II) is a brain metallopeptidase that hydrolyzes the abundant neuropeptide N-acetyl-aspartyl-glutamate (NAAG) to NAA and glutamate. Small molecule GCP-II inhibitors

Neonatal exposure to MK‐801 reduces mRNA expression of mGlu3 receptors in the medial prefrontal cortex of adolescent rats

It is suggested that NMDA‐R antagonism in the early course of development modulates the expression of mGluR3 in mPFC around puberty, which may serve as a potential target to prevent the onset and progression of schizophrenia.



Retracted: Neuroprotection mediated by glial group‐II metabotropic glutamate receptors requires the activation of the MAP kinase and the phosphatidylinositol‐3‐kinase pathways

Results suggest that activation of glial mGlu2/3 receptors induces neuroprotection through the activation of the MAPK and PI‐3‐K pathways leading to the induction of TGF‐β.

Dopamine D2‐type agonists protect mesencephalic neurons from glutamate neurotoxicity: Mechanisms of neuroprotective treatment against oxidative stress

It is demonstrated that preincubation with D2‐type dopamine agonists bromocriptine and quinpirole provides neuroprotection against glutamate‐induced neurotoxicity in cultured rat mesencephalic neurons and indicates that dopamine D2 agonists provide protection mediated not only by the inhibition of dopamine turnover but also via D2-type dopamine receptor stimulation and the subsequent synthesis of proteins that scavenge free radicals.

Activation of A1 adenosine or mGlu3 metabotropic glutamate receptors enhances the release of nerve growth factor and S‐100β protein from cultured astrocytes

It is concluded that activation of A1 adenosine or mGlu3 receptors produces pleiotropic effects in astrocytes, stimulating the synthesis and/or the release of protein factors.

High glucose‐induced oxidative stress and mitochondrial dysfunction in neurons

  • J. RussellD. Golovoy E. Feldman
  • Biology
    FASEB journal : official publication of the Federation of American Societies for Experimental Biology
  • 2002
The results indicate that mild increases in glucose induce ROS and Mt swelling that precedes neuronal apoptosis, and glucoseotoxicity is blocked by inhibiting ROS induction, MMD, or caspase cleavage by specific inhibitors of electron transfer, or by stabilizing the ANT.

Neuroprotection by Glial Metabotropic Glutamate Receptors Is Mediated by Transforming Growth Factor-β

It is concluded that a transient activation of group-II mGlu receptors (presumably mGLU3 receptors) in astrocytes leads to an increased formation and release of TGFβ, which in turn protects neighbor neurons against excitotoxic death.

N‐Acetylaspartylglutamate Inhibits Forskolin‐Stimulated Cyclic AMP Levels via a Metabotropic Glutamate Receptor in Cultured Cerebellar Granule Cells

Abstract: The neuronal dipeptide N‐acetylaspartylglutamate (NAAG) fulfills several of the criteria for classification as a neurotransmitter including localization in synaptic vesicles,

The Neuroprotective Activity of Group-II Metabotropic Glutamate Receptors Requires New Protein Synthesis and Involves a Glial–Neuronal Signaling

It is concluded that neuroprotection mediated by group-II mGlu receptors in cultured cortical cells requires new protein synthesis and involves an interaction between neurons and astrocytes.